| For medical practitioners and the general public - Cholesterol Journal Article Catalog. |
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| Thermotropic phase properties of the hydroxyceramide/cholesterol system Wiedmann, T. S. and A. Salmon (1991), Lipids 26(5): 364-8. Abstract: The interaction of cholesterol with ceramides containing alpha-hydroxy fatty acyl chains (hydroxyceramides) has been studied as a foundation for characterizing the lipid bilayers of the stratum corneum. A relatively large quantity of cerebrosides was obtained from bovine brain and converted to ceramides through removal of the carbohydrate side chain. The ceramides were separated based on the absence or presence of hydroxy fatty acyl chains. The lyophilized hydroxyceramides showed a broad melting region at 92 degrees C. Hydroxyceramides dispersed in water produced a relatively narrow, thermotropic transition at 75 degrees C. The effect of cholesterol on this thermotropic phase transition of hydroxyceramides was determined by differential scanning calorimetry. With respect to the main transition, cholesterol caused a broadening of the phase transition at relatively low levels as well as a decrease in the peak transition temperature. The presence of cholesterol at levels in excess of 7 wt% gave rise to an additional low-temperature transition at 55 degrees C. Upon immediate rescanning, this transition was exothermic, but with increasing incubation time the area under the excess heat capacity curve as a function of temperature became smaller. After two days or more, the transition observed was endothermic. At cholesterol levels between 40 and 50 wt%, multiple peaks were observed. From comparisons with related systems, the cooperative thermal transitions of hydroxyceramides with cholesterol are suggested to result from changes in hydrogen bonding or be due to phase separation. The composition of isolated brain ceramides is being compared with that reported for the stratum corneum. |
| Thermotropic properties of dispersions of cholesterol with tetraether lipids from Thermoplasma acidophilum Blocher, D., H. J. Freisleben, et al. (1991), Arch Biochem Biophys 290(1): 224-8. Abstract: The main glycophospholipid from Thermoplasma acidophilum is composed of a diisopranol-2,3-glycerotetraether. The fraction of pentane cyclizations of its hydrocarbon chains increases with the growth temperature of the source organism (39-59 degrees C). Hydrated mixtures of these lipids together with cholesterol have been studied by calorimetry. With the reduction of the phase transition temperatures and enthalpy changes of the transitions, cholesterol is readily incorporated into lipid monolayers in the liquid-crystalline and the (metastable) solid-analogue phase. Lipid samples with a high number of acyclic hydrocarbon chains form a stable and a metastable solid-analogue phase. With the increasing concentration of cholesterol the metastable solid-analogue phase is stabilized and the time constant for the formation of the stable solid-analogue phase is prolonged. |
| Thin-layer chromatography to monitor cholesterol gallstone dissolution by methyl tert-butyl ether D'Agostino, H. B., E. vanSonnenberg, et al. (1991), AJR Am J Roentgenol 157(1): 33-6. Abstract: We describe a simple and inexpensive method of monitoring methyl tert-butyl ether (MTBE) dissolution of cholesterol gallstones with thin-layer chromatography (TLC) in 10 patients. TLC is a routine semiquantitative laboratory method that can be used to measure the cholesterol concentration present in the MTBE and bile mixture aspirated through the cholecystostomy catheter during gallstone dissolution. TLC is practical in the clinical setting because it can be used to determine if gallstone dissolution is occurring and when MTBE lavage is no longer effective. TLC is performed in the laboratory with routine material and is completed in 15 min. Each TLC measurement costs about $1. The procedure provides objective and specific chemical information on effectiveness and progression of gallstone dissolution, apart from the radiologic and sonographic studies. In our study, TLC signaled effective dissolution in the initial phase of gallstone dissolution by detecting large amounts of cholesterol in the MTBE and bile mixture even before a visible change in size or shape of the stone became apparent by transcatheter cholecystography or by sonography (six of 10 patients). Conversely, lack of cholesterol on TLC after 1 hr or more of MTBE infusion indicates that the stones are pigmented or contain substantial calcium. This means that dissolution with MTBE will be ineffective and that solvent infusion should be terminated. In those cases in which dissolution is progressing well, when TLC shows decreasing amounts of cholesterol in the effluent, only residual fragments insoluble to MTBE remain or the stone is sequestered from MTBE; at this point, solvent infusion should be discontinued or the catheter must be repositioned. Monitoring the rate of cholesterol dissolution by TLC provides important complementary information to cholecystography and sonography during gallstone treatment with MTBE. |
| Thiol-independent activity of a cholesterol-binding enterohemolysin produced by enteropathogenic Escherichia coli Figueiredo, P. M., C. F. Catani, et al. (2003), Braz J Med Biol Res 36(11): 1495-9. Abstract: Enterohemolysin produced by Escherichia coli associated with infant diarrhea showed characteristics similar to those of thiol-activated hemolysins produced by Gram-positive bacteria, including inactivation by cholesterol, lytic activity towards eukaryotic cells and thermoinstability. However, enterohemolysin activity was not inactivated by oxidation or by SH group-blocking agents (1 mM HgCl2, 1 mM iodoacetic acid) and the hemolysin (100 microg/ml) was not lethal to mice, in contrast to the lethality of the thiol-activated hemolysin family to animals. Earlier reports showed that intravenous injection of partially purified streptolysin O preparations (0.2 microg) was rapidly lethal to mice. These results suggest that E. coli enterohemolysin is not a thiol-activated hemolysin, despite its ability to bind cholesterol, probably due to the absence of free thiol-group(s) that characterize the active form of the thiol-activated hemolysin molecule. |
| Threat of unemployment and cardiovascular risk factors: longitudinal study of quality of sleep and serum cholesterol concentrations in men threatened with redundancy Mattiasson, I., F. Lindgarde, et al. (1990), Bmj 301(6750): 461-6. Abstract: OBJECTIVE--To assess whether the threat of unemployment affects risk factors for cardiovascular disease. DESIGN--Longitudinal study of a cohort of middle aged shipyard workers followed up for a mean of 6.2 (SD 1.9) years and a group of controls observed for the same period. The first investigation took place during a period of relative economic stability for the shipyard and the second during the phase of its closure. SETTING--An age cohort health screening programme in Malmo, Sweden. PARTICIPANTS--715 Male shipyard workers and 261 age matched male controls. MAIN OUTCOME MEASURES--Changes in 19 variables related to the risk of cardiovascular disease, and psychological variables, alcohol consumption, smoking, and dietary habits as assessed by questionnaire. RESULTS--Serum cholesterol concentrations increased more (mean 0.25 (SD 0.68) mmol/l v 0.08 (0.66) mmol/l) and serum calcium concentrations decreased less (-0.06 (0.10) mmol/l v -0.08 (0.09) mmol/l) in the shipyard workers than in the controls. A correlation was found between scores for sleep disturbance and changes in serum cholesterol concentration. In the whole series there was a greater increase in serum cholesterol concentrations among men threatened with unemployment (437/976; 44.8%) than among those who were not. In stepwise regression analysis the change in serum cholesterol concentration was correlated with changes in haemoglobin concentration, body weight, and serum triglyceride and calcium concentrations. A positive correlation was found between change in cholesterol concentration and change in blood pressure, indicating that the overall risk profile had worsened among men with increased serum cholesterol concentrations. CONCLUSIONS--Risk of unemployment increases the serum cholesterol concentration in middle aged men, the increase being more pronounced in those with sleep disturbance. The increase in serum cholesterol is related to changes in other established risk factors for cardiovascular disease. These findings might partly explain the excessive mortality due to cardiovascular disease recorded among the unemployed and people with sleep disturbance. |
| Three generations of high-density lipoprotein cholesterol assays compared with ultracentrifugation/dextran sulfate-Mg2+ method Harris, N., V. Galpchian, et al. (1997), Clin Chem 43(5): 816-23. Abstract: We report on the analytical performance of three generations of HDL-cholesterol assays: phosphotungstic acid/Mg2+, Spinpro, and a homogeneous method, N-geneous. The run-to-run imprecision (CV) of all assays was < or = 4.9%, and all results correlated highly with those of a modified reference procedure (r > or = 0.96). At triglycerides concentrations < 4000 mg/L, these field methods showed an acceptable systematic error (y = 1.12x - 47, 1.05x - 23, and 0.96x + 8 for the phosphotungstate, Spinpro, and N-geneous assays, respectively), and the total error of the field methods met the current National Cholesterol Education Program (NCEP) performance goal of < or = 22%. Regression analyses of results for samples with triglycerides > 4000 mg/L produced the following results for the above respective assays: y = 1.08x - 4.2, 1.02x + 3.6, and 0.85x + 108. In this hypertriglyceridemic group, only the N-geneous assay (at an HDL-cholesterol content of 240 mg/L) had a total error (35%) that exceeded the NCEP limit. Bilirubin and ascorbate produced a negative interference with the phosphotungstate and Spinpro assays but had little effect on the N-geneous assay. |
| Three lipoprotein receptors and cholesterol in inclusion-body myositis muscle Jaworska-Wilczynska, M., G. M. Wilczynski, et al. (2002), Neurology 58(3): 438-45. Abstract: BACKGROUND: An important aspect of inclusion-body myositis (IBM) vacuolated muscle fibers (VMF) is abnormal accumulation of amyloid-beta precursor protein (AbetaPP) epitopes and its product, amyloid-beta (Abeta), and of phosphorylated tau (p-tau) in the form of paired helical filaments. Lipoprotein receptors and cholesterol are known to play an important role in AbetaPP processing, Abeta production, and tau phosphorylation. METHODS: In 10 IBM and 22 control muscle biopsies the authors immunolocalized low-density lipoprotein receptor (LDLR), very low-density lipoprotein receptor (VLDLR), and low-density lipoprotein receptor-related protein (LRP), and colocalized them with Abeta, p-tau, APOE, and free cholesterol. RESULTS: In each biopsy, virtually all IBM VMF had strong LDLR-immunoreactive inclusions, which colocalized with Abeta, APOE, p-tau, and free cholesterol. VLDLR was increased mainly diffusely, but in approximately 50% of the VMF it was also accumulated in the form of inclusions colocalizing with Abeta, APOE, and free cholesterol, but not with p-tau. LRP inclusions were present in a few VMF. In all myopathies, a subset of regenerating and necrotizing muscle fibers had prominent diffuse accumulation of both LDLR and free cholesterol. At normal neuromuscular junctions (NMJ) postsynaptically, LDLR and VLDLR, but not LRP, were immunoreactive. CONCLUSIONS: 1) Abnormal accumulation of LDLR, VLDLR, LRP, and cholesterol within IBM vacuolated muscle fibers suggests novel roles for them in the IBM pathogenesis. 2) Expression of LDLR and VLDLR at normal NMJ suggests physiologic roles for them in transsynaptic signaling pathways, increased internalization of lipoproteins there, or both. 3) Increased LDLR and free cholesterol in some regenerating and necrotizing muscle fibers suggest a role for them in human muscle fiber growth and repair and necrotic death. |
| Three routine methods for measuring high-density lipoprotein cholesterol compared with the Reference Method Harris, N., V. Galpchian, et al. (1996), Clin Chem 42(5): 738-43. Abstract: We compared the performance of three methods for quantifying high-density lipoprotein cholesterol (HDL-C) with the Reference Method for HDL-C, using samples with a wide range of triglyceride (TG) concentrations (290-18000 mg/L). All three comparison assays-- utilizing a magnetic dextran sulfate precipitating reagent, a direct method, and a standard MgCl2-dextran sulfate reagent--were precise, with a run-to-run CV of less than or equal to 4.1%. However, the systematic error of these assays exceeded the National Cholesterol Education Program (NCEP) performance goal of less than or equal to 10% in half of the concentration ranges tested. Nevertheless, the total error of the assays generally meets the current 22% limit set by the NCEP. Although both the magnetic dextran sulfate precipitation reagent and the direct assay can be performed more rapidly than the MgCl2-dextran sulfate assay, the direct assay involves no sample preparation and requires only 4 microL of sample excluding the dead space. Although precipitation is frequently inadequate with the MgCl2-dextran sulfate reagent at TG concentrations >6000 mg/L, both the magnetic and the direct reagent show no interference from high TG concentrations as great as 18 000 mg/L. |
| Three-minute whole-blood cholesterol screening test evaluated Pradella, M., G. Mantovani, et al. (1990), Clin Chem 36(11): 1994-5. |
| Three-year follow-up of the Oxford Cholesterol Study: assessment of the efficacy and safety of simvastatin in preparation for a large mortality study Keech, A., R. Collins, et al. (1994), Eur Heart J 15(2): 255-69. Abstract: We report the results of a randomized single-centre study designed to assess the effects of simvastatin on blood lipids, blood biochemistry, haematology and other measures of safety and tolerability in preparation for a large-scale multicentre mortality study. Six hundred and twenty-one individuals considered to be at increased risk of coronary heart disease were randomized, following a 2-month placebo 'run-in' period, to receive 40 mg daily simvastatin, 20 mg daily simvastatin or matching placebo. Their mean age was 63 years, 85% were male, 62% had a history of prior myocardial infarction (MI), and the mean baseline total cholesterol was 7.0 mmol.l-1. Median follow-up in the present report is 3.4 years. Eight weeks after randomization, 40 mg daily simvastatin had reduced non-fasting total cholesterol by 29.2% +/- 1.1 (2.03 +/- 0.08 mmol.l-1) and 20 mg daily simvastatin had reduced it by 26.8% +/- 1.0 (1.87 +/- 0.07 mmol.l-1). Almost all of the difference in total cholesterol at 8 weeks was due to the reduction in LDL cholesterol (40.8% +/- 1.6 and 38.2% +/- 1.4 among patients allocated 40 mg and 20 mg of simvastatin daily respectively), but simvastatin also reduced triglycerides substantially (19.0% and 17.3%) and produced a small increase in HDL cholesterol (6.4% and 4.8%). These effects were largely sustained over the next 3 years, with 40 mg daily simvastatin producing a slightly greater reduction in total cholesterol at 3 years (25.7% +/- 1.9 reduction) than did 20 mg daily simvastatin (22.2% +/- 1.8). There were no differences between the treatment groups in the numbers of reports of 'possible adverse effects' of treatment or of a range of different symptoms or conditions (including those related to sleep or mood) recorded at regular clinic follow-up. Mean levels of alanine aminotransferase, aspartate aminotransferase and creatine kinase were slightly increased by treatment, but there were no significant differences between the treatment groups in the numbers of patients with significantly elevated levels. A slightly lower platelet count in the simvastatin group was the only haematological difference from placebo, with no difference in the numbers of patients with low platelet counts. In summary, the simvastatin regimens studied produced large sustained reductions in total cholesterol, LDL cholesterol and triglyceride and small increases in HDL cholesterol. They were well tolerated, with no evidence of serious side-effects during the first 3 years of this study.(ABSTRACT TRUNCATED AT 400 WORDS) |
| Thresholds for normal blood pressure and serum cholesterol Westin, S. and I. Heath (2005), Bmj 330(7506): 1461-2. |
| Thyroid function and cholesterol level: paradoxical findings in large groups of population with high cholesterol food intake Langer, P., A. Kocan, et al. (2003), Endocr Regul 37(3): 175-80. Abstract: OBJECTIVE: To compare the levels of serum cholesterol with thyroid function as estimated by the level of thyrotropin and free thyroxine with possible participation of thyroperoxidase antibodies in large number of adults examined within large field surveys focused on the evaluation of thyroid status of Slovak rural population. SUBJECTS AND METHODS: Serum level of cholesterol and thyrotropin (TSH) was estimated in a total of 2786 adults. In addition, in 2038 of them also the level of free thyroxine (FT4), total triiodothyronine (TT3), cholesterol, triglycerides and phospholipids was measured. The levels of TSH, anti-TPO and FT4 were estimated by supersensitive electrochemiluminiscent immunoassay using the automatic system Elecsys (Roche, Switzerland). RESULTS: A total of 2786 adults was stratified into 7 groups according to the range of TSH level as related to generally recognized level of thyroid function, e.g. 1. TSH <0.10 mU/L (overt hyperthyroidism, N=41), 2. TSH 0.11-0.30 mU/L (overt or subclinical hyperthyroidism, N=149), 3. TSH 0.31-2.50 mU/L (normal level, N=1750), 4. TSH 2.51-4.50 ("high normal" level, N=607), 5 TSH 4.51-6.50 (mild or incipient subclinical hypothyroidism, N=137), 6. TSH 6.51-10.00 mU/L (mild hypothyroidism, N=50), 7. TSH 10.01-99.00 mU/L (severe hypothyroidism, N=53). The average levels of cholesterol in all groups were very similar ranging from 5.53 to 6.17 mmol/L and no interrelations with TSH level were found. In addition, no considerable differences between these groups were found when considering the levels of medians, upper quartiles and 90th percentiles of individual groups. When male and female subjects were divided into age groups according to the decades, an age dependent increase of cholesterol level was found in both sexes. The fraction of 2038 subjects was divided into the same TSH related groups as defined above. Similarly as above, no considerable differences in cholesterol, triglycerides and phospholipids level were observed. However, the levels of FT4 and TT3 were significantly decreasing with the increase of TSH level which confirmed the continuing decrease of thyroid function. The frequency of positive anti-TPO in subjects with TSH >6.5 mU/l (71/86 = 82.5%) was significantly higher than that in subjects with TSH <6.5 mU/l (468/1952 = 23.9%). CONCLUSIONS: No difference in the level of cholesterol and triglycerides was found in large groups of rural adults from Slovakia with various thyroid function as estimated by the level of TSH, FT4, TT3 and anti-TPO. It is assumed that this interrelation resulted from very high cholesterol intake due to inappropriate general nutritional status of rural population resulting from the consumption of unhealthy foods. |
| Thyroid hormone is required for dietary fish oil to induce hypersecretion of biliary cholesterol in the rat Prigge, W. F., S. R. Ketover, et al. (1995), Lipids 30(9): 833-8. Abstract: In the rat, both fish oil diet and thyroid hormone replacement are reported to augment bile cholesterol secretion out of proportion to bile flow or secretion of other bile lipids. We sought common mechanisms for these effects and evaluated the role of phospholipid fatty acid composition in the process. Methimazole-treated hypothyroid rats were fed low-fat chow or chow supplemented with 10% corn oil or fish oil, and were studied before and after thyroid hormone treatment. Serum, hepatic, and bile lipids were measured, phospholipid fatty acid composition determined, and hepatic 3-hydroxy-3-methylglutaryl CoA reductase activity assayed. Fish oil diet stimulated cholesterol secretion into bile only after thyroid hormone was given, and this action was synergistic with that of thyroid hormone. Reduced serum cholesterol in fish oil-treated rats was associated with increased biliary cholesterol secretion and diminished hepatic cholesterol content. This suggests that augmented biliary cholesterol secretion may contribute to the fish oil-induced reduction of serum cholesterol. No definite relationship between hepatic or biliary phospholipid fatty acid composition and biliary secretion was apparent, although high bile cholesterol secretion was associated with a low percentage of hepatic and bile phospholipid linoleic acid. |
| Thyroid hormone receptor beta-deficient mice show complete loss of the normal cholesterol 7alpha-hydroxylase (CYP7A) response to thyroid hormone but display enhanced resistance to dietary cholesterol Gullberg, H., M. Rudling, et al. (2000), Mol Endocrinol 14(11): 1739-49. Abstract: Thyroid hormone (T3) influences hepatic cholesterol metabolism, and previous studies have established an important role of this hormone in the regulation of cholesterol 7alpha-hydroxylase (CYP7A), the rate-limiting enzyme in the synthesis of bile acids. To evaluate the respective contribution of thyroid hormone receptors (TR) alpha1 and beta in this regulation, the responses to 2% dietary cholesterol and T3 were studied in TRalpha1 and TRbeta knockout mice under hypo- and hyperthyroid conditions. Our experiments show that the normal stimulation in CYP7A activity and mRNA level by T3 is lost in TRbeta-/- but not in TRalpha1-/-mice, identifying TRbeta as the mediator of T3 action on CYP7A and, consequently, as a major regulator of cholesterol metabolism in vivo. Somewhat unexpectedly, T3-deficient TRbeta-/- mice showed an augmented CYP7A response after challenge with dietary cholesterol, and these animals did not develop hypercholesterolemia to the extent as did wild-type (wt) controls. The latter results lend strong support to the concept that TRs may exert regulatory effects in vivo independent of T3. |
| Thyroid hormone regulation and cholesterol metabolism are connected through Sterol Regulatory Element-Binding Protein-2 (SREBP-2) Shin, D. J. and T. F. Osborne (2003), J Biol Chem 278(36): 34114-8. Abstract: High affinity uptake of serum-derived low density lipoprotein (LDL) cholesterol is accomplished through the LDL receptor in the liver. In mammals, thyroid hormone depletion leads to decreased LDL receptor expression and elevated serum cholesterol. The clinical association in humans has been known since the 1920s; however, a molecular explanation has been lacking. LDL receptor levels are subject to negative feedback regulation by cellular cholesterol through sterol regulatory element-binding protein-2 (SREBP-2). Here we demonstrate that the SREBP-2 gene is regulated by thyroid hormone and that increased SREBP-2 nuclear protein levels in hypothyroid animals results in thyroid hormone-independent activation of LDL receptor gene expression and reversal of the associated hypercholesterolemia. This occurs without effects on other thyroid hormone-regulated genes. Thus, we propose that the decreased LDL receptor and increased serum cholesterol associated with hypothyroidism are secondary to the thyroid hormone effects on SREBP-2. These results suggest that hypercholesterolemia associated with hypothyroidism can be reversed by agents that directly increase SREBP-2. Additionally, these results indicate that mutations or drugs that lower nuclear SREBP-2 would cause hypercholesterolemia. |
| Tibolone lowers high density lipoprotein cholesterol by increasing hepatic lipase activity but does not impair cholesterol efflux von Eckardstein, A., D. Crook, et al. (2003), Clin Endocrinol (Oxf) 58(1): 49-58. Abstract: OBJECTIVE: Androgens and other drugs that reduce plasma concentrations of high density lipoprotein (HDL) cholesterol are often considered to be pro-atherogenic. Tibolone lowers HDL-cholesterol by 20% but the clinical significance of this effect is unknown. METHODS: In a randomized, double-blind study, 34 women received 2.5 mg tibolone daily and 34 women received placebo. Serum concentrations of lipids, lipoprotein subclasses and apolipoproteins, together with plasma activities of lipid transfer proteins and lipolytic enzymes and the capacity of plasma to induce cholesterol efflux from cultured cells, were measured. RESULTS: Compared to placebo, tibolone reduced serum concentrations of HDL-cholesterol (-14%), HDL phosphatidylcholine (-14%), apolipoprotein (apo)A-I (-12%), HDL subclasses lipoprotein (Lp)A-I (-20%), HDL-apoE (-16%), pre beta-LpA-I (-10%) and alpha-LpA-I (-12%) and increased hepatic lipase activity (+25%) and HDL sphingomyelin: phosphatidylcholine ratio (10.5%), but did not alter serum concentrations of HDL sphingomyelin, apoA-IV and LpA-I/A-II, lipoprotein lipase, the plasma activities of lecithin: cholesterol acyl transferase, cholesteryl ester transfer protein, phospholipid transfer protein or the plasma capacity to release cholesterol from cultured fibroblasts or Fu5AH hepatocytes. CONCLUSIONS: Tibolone lowers HDL-cholesterol in part by increasing hepatic lipase activity. Conservation of sphingomyelin and apoA-II in HDL, as well as cholesteryl ester transfer protein activity, preserves the capacity of plasma to release cholesterol, despite the lower concentrations of HDL-cholesterol. This may have important implications for the use of steroid effects on HDL concentrations as surrogates for atherosclerosis. |
| Tibolone prevents atherosclerotic lesion formation in cholesterol-fed, ovariectomized rabbits Zandberg, P., J. L. Peters, et al. (1998), Arterioscler Thromb Vasc Biol 18(12): 1844-54. Abstract: Tibolone (Org OD14), a synthetic steroid with estrogenic and progestogenic/androgenic properties, is clinically effective for the treatment of climacteric symptoms and the prevention and treatment of osteoporosis in postmenopausal women. The effect on atherogenesis, however, is not known. In the current study, we investigated the effect of tibolone in comparison with that of estradiol and norethisterone acetate on atherogenesis in 140 ovariectomized New Zealand White rabbits that had been induced by an atherogenic diet (0.4% cholesterol, 20 weeks). Tibolone at 18, 6, or 2 mg/d orally completely prevented cholesterol accumulation and fatty streak formation in the aorta; the impairment of endothelium-dependent smooth muscle relaxation of the aorta; and complex lesion formation after endothelial denudation in the carotid artery. Tibolone also reduced the increased postovariectomy plasma lipid concentrations. Analysis of the results, however, indicated that a substantial part of the strong, beneficial effects were plasma lipid independent. Compared with subcutaneous estradiol decanoate (150 microgram once weekly) and oral 17beta-estradiol (4 mg/d), the effects of tibolone were more pronounced at equipotent uterotropic activity. Norethisterone acetate (1 mg/d) did not affect atherosclerotic lesion formation. There are no indications that the progestogenic/androgenic properties of tibolone counteracted its atheroprotective effect on the vessel wall. Therefore, tibolone has the intrinsic potential to be a compound that protects the arterial vessel wall against atherosclerotic processes. |
| Time course and cellular characteristics of the iliac artery response to acute balloon injury. An angiographic, morphometric, and immunocytochemical analysis in the cholesterol-fed New Zealand white rabbit Stadius, M. L., R. Rowan, et al. (1992), Arterioscler Thromb 12(11): 1267-73. Abstract: Evaluation of the response of the arterial vessel wall to acute arterial injury in experimental models has taken on substantial importance because of an increasing interest in angioplasty treatment of human atherosclerotic lesions. In this study, the response of normal arterial vessels to acute balloon injury was studied in 45 iliac artery segments from 24 New Zealand White rabbits fed a 2% cholesterol diet. At specified time points between 1 and 41 days after the initial balloon pullback injury, the iliac arteries were analyzed by angiographic, morphometric, and immunocytochemical techniques. Angiographic measurements indicated progressive compromise of the iliac artery lumen with increasing duration of time from injury. Morphometric measurements showed that intimal area increased from 0.004 +/- 0.01 mm2 3 days after injury to 1.15 +/- 0.30 mm2 34-41 days after injury. Cell line-specific immunocytochemical analysis identified the macrophage as a prominent component of the earliest intimal cellular infiltrate. Smooth muscle cells appeared within the intima 7-9 days after injury. As the intima increased in area, macrophages predominated along the internal elastic lamina aspect of the intimal lesion while smooth muscle cells occupied the portion of the intima adjacent to the lumen. In summary, retrograde balloon pullback injury followed by cholesterol feeding results in progressive arterial luminal narrowing due to a progressively enlarging intimal cellular infiltrate. The temporal and spatial contributions of smooth muscle cell and macrophage components of the developing intimal cellular infiltrate have been characterized. |
| Time course of changes in rat serum lecithin-cholesterol acyl-transferase activity and high-density-lipoprotein composition during the consumption of two different low-protein diets followed by a balanced diet Lamri, M. Y., M. Meghelli-Bouchenak, et al. (1995), Nutrition 11(5): 444-9. Abstract: We studied the effects of low-protein diets on high-density-lipoprotein (HDL) composition and checked whether the changes observed were correlated with lecithin-cholesterol acyl-transferase (LCAT) activity. We also studied whether HDL lipid and protein compositions and LCAT activity were modified differently in growing rats during the consumption of two low-protein diets 2% casein (C) and 5% gluten (GI) for 28 days, followed by the refeeding of a balanced diet containing 15% casein for 14 days. The control group was fed the balanced diet for 42 days. LCAT activity was determined by conversion of 3H-cholesterol into 3H-esterified cholesterol. The consumption of both protein-depleted diets highly decreased LCAT activity. At the end of the period of protein malnutrition, LCAT activity was only 22% and 13% of that of the control group in the C and GI groups, respectively. There was no significant difference between the two depleted diets. At day 3 of refeeding, values of both C and GI groups returned to control values. Despite the reduction in LCAT activity with both types of protein-depleted diets, HDL metabolism was not significantly impaired. This might be partly due to the maintenance of higher apolipoprotein A-I levels. The reduced LCAT activity could be attributable to reduced synthesis of LCAT in the liver during both protein-depleted diets. |
| Time dependent changes in the concentration and type of bacterial sequences found in cholesterol gallstones Swidsinski, A., M. Khilkin, et al. (1998), Hepatology 27(3): 662-5. Abstract: The role of bacteria in gallstone formation could not be conclusively evaluated until bacterial presence or absence in a stone was consistently shown. Cultural bacteriologic investigations at the time of cholecystectomy, however, led to the assumption that cholesterol gallstones were free of bacteria. In this study, we used a culture independent, molecular genetic approach to detect, quantify, and identify bacteria in cholesterol gallstones from 100 patients at the time of cholecystectomy and 6 months following. Bacterial growth was recorded in the culture in 9 of 100 gallstones; bacterial DNA, however, was detected in 82 of 91 sterile gallstones. High concentrations corresponding to between 10(6) to 10(7) bacteria/g were detected in 11 stones and low concentrations of 10(5) bacteria/g were detected in 71 sterile stones. The infection in stones with a positive bacterial culture was characterized by the predominance of single bacterial sequence(s) of the bacteria cultured. A similar predominance, indicating a recent infection, was found in sterile gallstones with low DNA concentrations. A high diversity of non-repeating bacterial sequences, possibly arising from previous overlapping infections, was found in sterile gallstones with high concentrations of bacterial DNA. After 6 months concentrations of bacterial DNA fell significantly in all groups of gallstones. As bacterial DNA is quickly destroyed upon storage, but is nevertheless readily found in most gallstones at the time of cholecystectomy, there must be a mechanism by which it is replenished. One such mechanism is the frequently reoccurring, possibly self-terminating infection and another one is the permanent colonization of the gallstone with bacteria at low concentrations. Both can promote cholecystolithiasis. |